A Multicentre, Open Label, Phase 1 Trial in Japan of the Mitogen Activated Protein Extracellular Signal Regulated Kinase (MEK) Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy

NCT ID: NCT01668017

Last Updated: 2017-08-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2015-05-31

Brief Summary

This is a two-part trial. "Solid tumor" in this protocol means solid tumor excluding hepatocellular carcinoma (HCC).

Part 1: Dose Escalation Phase in subjects with solid tumor (Cohort A) and HCC (Cohort B). The dose will be increased from 45 mg twice a day (BID) with 3+3 cohort method up to the recommended phase 2 dose (RP2D) of pimasertib established as single agent in the global studies for each arm independently.

Part 2: The Maximum Tolerated Dose (MTD) defined in Part 1 will be confirmed in more subjects in Cohort A (N=18) and Cohort B (N=6) separately.

Following the recommendation by the Safety Monitoring Committee, Cohort B was discontinued due to hepatocellular carcinoma (HCC) and there will be no further enrollment of subjects to this cohort. This decision is based upon review of safety and efficacy information.

Conditions

Advanced Solid Tumors; Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Pimasertib 30mg in Solid Tumor

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects with solid tumor will be administered with Pimasertib 30 mg twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Part 1: Pimasertib 45 mg in Solid Tumor

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects with solid tumor will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Part 1: Pimasertib 60 mg in Solid Tumor

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects with solid tumor will be administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC)

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects with HCC will be administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Part 1: Pimasertib 45 mg in HCC

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects with HCC will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Interventions

Pimasertib

Subjects with solid tumor will be administered with Pimasertib 30 mg twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Intervention Type: DRUG

Pimasertib

Subjects with solid tumor will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Intervention Type: DRUG

Pimasertib

Subjects with solid tumor will be administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Intervention Type: DRUG

Pimasertib

Subjects with HCC will be administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Intervention Type: DRUG

Pimasertib

Subjects with HCC will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Cohort A: A histologically or cytologically confirmed diagnosis of advanced solid tumors which is either refractory after standard therapy for the disease or for which no effective standard therapy is available. Archived tumor tissue available or biopsy of tumor tissue needs to be performed.

Cohort B: A histologically or cytologically confirmed diagnosis of advanced hepatocellular carcinoma (HCC) which is either refractory after standard therapy for the disease or for which no effective standard therapy is available. Archived tumor tissue available or biopsy of tumor tissue needs to be performed. Subjects with Child Pugh A.

• Male or female Japanese, age greater than or equal to (>=) 18 years.
• Subject has read and understands the informed consent form and is willing and able to give informed consent. The subject fully understands requirements of the trial and is willing to comply with all trial visits and assessments.
• Women of childbearing potential must have a negative blood pregnancy test at the screening visit.
• Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose investigational medicinal product (IMP).
• Life expectancy of at least 3 months

Exclusion Criteria

Hematological abnormality Cohort A: Hematological test abnormalities of Hemoglobin < 9.0 g/dL, Neutrophil count < 1.0*10^9/L and Platelet count < 100*10^9/L.

Cohort B: Hematological test abnormalities of Hemoglobin < 9.0 g/dL, Neutrophil count < 1.0*10^9/L, Platelet count < 75*10^9/L, subjects with hepatic encephalopathy

• Renal impairment as evidenced by serum creatinine > 1.5*upper limit of normal (ULN), and calculated creatinine clearance < 60 mL/min by Cockcroft-Gault formula.
• Liver function abnormality of Total Bilirubin > 1.5*ULN, or aspartate transaminase 9AST) or alkaline phosphatase (ALT)> 2.5*ULN. For subjects with HCC or liver involvement AST/ALT > 5*ULN.
• History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases
• History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions
• Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than 1.
• Has received chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy (including any investigational agent) or surgical intervention within 28 days or 5 half lives for non-cytotoxics of registration.
• Baseline corrected QT interval on screening ECG (QTc) >= 480 ms or left ventricular ejection fraction (LVEF) < 40% on screening echocardiogram
• Cohort B: Subjects with hepatic encephalopathy, remarkable ascites and subjects with history of esophageal varices rupture within 6 months (subjects with symptom improvement after treatment are eligible)
• Other serious illness or medical conditions.
• Retinal degenerative disease.
• Previous treatment with MEK inhibitors.
• Legal incapacity or limited legal capacity.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Serono Co., Ltd., Japan

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Serono Co., Ltd., Tokyo, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

Please contact

Merck Serono Co., Ltd For Recruiting Locations in, , Japan

Countries

Japan

Other Identifiers

EMR 200066-010

Identifier Type: -

Identifier Source: org_study_id